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VEGF-A and Notch signaling pathways are key players governing tip and stalk cell behavior. Normal sprouting angiogenesis in the mouse retina requires a gradient of the pro-angiogenic factor VEGF-A. This local VEGF-A gradient is produced by the preformed astrocyte network that serves as a guiding scaffold for the developing retinal plexus. In fact, the tip cells are closely attached to the astrocytes, and their filopodia extend along the astrocytes toward higher VEGF-A concentrations in this gradient. Interestingly, if VEGF-A stimulation is blocked using sVEGFR1 or neutralizing the signaling through VEGFR2 with antibodies, the tip cell filopodia are completely retracted in the sprouting retinal front, preventing tip cell migration and thus progression of vascular sprouting seizes. In contrast, stimulation of quiescent vessels with VEGF-A induces filopodia formation and tip cell gene expression, together illustrating that VEGF-A is both necessary and sufficient to induce endothelial tip cells. Similar observations in zebrafishembryogenesis and other tissues in the mouse confirm the general importance of this concept.

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1樓 2014-04-06 23:11:06

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愛(ài)與雨下: 金幣+1 2014-04-08 21:06:10
cainiaodui: 金幣+15, 翻譯EPI+1 2014-04-08 21:27:28

VEGF-A和Notch信號(hào)通路是調(diào)節(jié)尖端細(xì)胞和干細(xì)胞反應(yīng)的關(guān)鍵。小鼠視網(wǎng)膜的正常出芽式血管新生要求促血管生成因子VEGF-A梯度。這一局部VEGF-A梯度由作為 ‎視網(wǎng)膜神經(jīng)叢發(fā)展導(dǎo)向支架的星形膠質(zhì)細(xì)胞網(wǎng)絡(luò)產(chǎn)生。事實(shí)上，尖端細(xì)胞緊附于星形膠質(zhì)細(xì)胞，并且它們的絲狀偽足沿星形膠質(zhì)細(xì)胞向更高的VEGF-A的濃度梯度方向延伸。有趣的是，如果用sVEGFR1阻斷VEGF-A刺激或抗體中和VEGFR2，尖端細(xì)胞絲狀偽足在芽生視網(wǎng)膜前完全收縮，阻止根尖細(xì)胞的遷移，從而抑制血管發(fā)芽進(jìn)程。相反，VEGF - A刺激靜止血管則誘導(dǎo)絲狀偽足形成以及尖端細(xì)胞的基因表達(dá)，正反兩方面的實(shí)驗(yàn)表明VEGF-A必要性并且足以誘導(dǎo)內(nèi)皮尖端細(xì)胞。斑馬魚(yú)胚胎發(fā)育和小鼠其他組織發(fā)育也觀察到類似的情況，證實(shí)了這一概念具有普遍重要性。

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2樓2014-04-08 16:54:42

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